Growth hormone releasing factor (GRF) has been isolated from human islet cell tumor and structurally characterized by Guillemin et al. at the Salk Institute. Science 218: 585 (1982). The isolation and characterization of GRF eluded researchers for decades because the polypeptide was present in tissues in very small quantities. Human hypothalamic growth hormone releasing factor (hGRF) has been found to have the same structure as GRF isolated from islet cell tumor. Bohlen et al., Biochem. Biophys. Res. Commun. 114: 930 (1983).
Rivier et al., Nature 300: 276 (1982) have described the structure of GRF (1-44) and GRF (1-40) and have shown that GRF is specific for the release of growth hormone. These two forms of GRF are identical at the amino (NH.sub.2 -) terminus but differ in length. GRF (1-44) is further distinguished by the presence of an amide group at the carboxy terminus.
Rivier et al., supra, have shown that the biological activity of GRF resides in the NH.sub.2 -terminal portion of the molecule; full intrinsic activity and potency on a weight for weight basis was demonstrated with GRF(1-29)-NH.sub.2 in vitro.
Lance et al., Biochem. Biophys. Res. Commun. 119: 265 (1984) have shown that GRF (1-29)-NH.sub.2 having substitutions of selected amino acids at positions 1, 2 and 3 causes enhanced release of growth hormone (GH) in both pigs and rats in vivo. U.S. Pat. No. 4,518,586 discloses various GRF synthetic peptides, including one in which there is the substitution of D-Ala at position 15 for Gly. Similarly U.S. Pat. Nos. 4,528,190 and 4,529,595 disclose various GRF analogs, including the substitution of D-Ala at position 15 and Asn at position 28.
It is believed that growth in animals is regulated by a cascade of bioregulatory molecules. The hypothalamus produces GRF, which induces the release of growth hormone from the pituitary. Small quantities of GRF have been found to cause substantial pituitary release of growth hormone into the blood. Thus, GRF has great therapeutic utility in those instances where growth hormone administration is indicated. For example, GRF may be used in the treatment of hypopituitary dwarfism, diabetes due to growth hormone production abnormalities, promotion of wound and bone fracture healing, treatment of burns and retardation of the aging process. Similarly GRF has utility in the agricultural field. Examples of agricultural uses include enhanced meat production of fowl or animals raised for food such as pigs, cattle or the like to permit earlier marketing or to produce larger animals kept for similar time on feed, or improve the lean to fat ratios. GRF may also stimulate milk production in dairy cows and egg production in chickens.